Search

US-12616666-B2 - Coenzyme Q10 formulations in the treatment and prevention of epidermolysis bullosa

US12616666B2US 12616666 B2US12616666 B2US 12616666B2US-12616666-B2

Abstract

The present invention is directed, in part, to methods of treating Epidermolysis Bullosa (EB) in a subject in need thereof, comprising topical administration of a pharmaceutical composition comprising a therapeutically effective amount of a of Coenzyme Q10 (CoQ10) to the subject.

Inventors

  • Niven Rajin Narain
  • Rangaprasad Sarangarajan
  • Michael Andrew Kiebish

Assignees

  • BPGBIO, INC.

Dates

Publication Date
20260505
Application Date
20220713

Claims (10)

  1. 1 . A method of treating Epidermolysis Bullosa (EB) in a subject having one or more wounds associated with the EB between 2.5 cm 2 and 50 cm 2 in size, comprising topically administering a pharmaceutical composition comprising a therapeutically effective amount of Coenzyme Q10 (CoQ10) to the subject, thereby reducing the size of the one or more wounds associated with the EB.
  2. 2 . The method of claim 1 , wherein the Epidermolysis Bullosa is Epidermolysis Bullosa Simplex, Junctional Epidermolysis Bullosa, Dystrophic Epidermolysis Bullosa, or Kindler's Syndrome.
  3. 3 . The method of claim 1 , wherein the pharmaceutical composition comprising CoQ10 is administered for a treatment duration from about one week to about twelve weeks.
  4. 4 . The method of claim 1 , wherein the pharmaceutical composition comprising CoQ10 is administered to the subject from 1 to about 14 times per week for the treatment duration.
  5. 5 . The method of claim 1 , wherein the pharmaceutical composition comprising CoQ10 contains from about 1% to about 5% CoQ10 (w/w).
  6. 6 . The method of claim 1 , wherein administering the pharmaceutical composition comprising CoQ10 to the subject provides one or more beneficial effects to the subject, wherein the one or more beneficial effects is selected from the group consisting of: a. Reduction in pain associated with the EB; b. Reduction in inflammation associated with the EB; c. Reduction in the number of blisters and/or wounds associated with the EB; d. Increase in the rate of healing of one or more blisters and/or wounds associated with the EB; e. Increase in the structural integrity of the skin of the subject suffering from EB; f. Reduction in the number of skin infections associated with EB; g. Increase in wound closure of wounds associated with EB; h. Increase in re-epithelization of wounds associated with EB; i. Increase in granulation of wounds associated with EB; j. Reduction in an epidermal gap distance of a blister and/or wound associated with EB; k. Reduction in time for blister and/or wound healing associated with EB; l. Reduction in the amount of concomitant medications administered to the subject in order to treat the subject's EB; m. Reduction in scarring associated with EB; n. Increase in keratinocyte production in the skin of the subject; and o. Increase in fibroblast production in the skin of the subject.
  7. 7 . The method of claim 1 , wherein the pharmaceutical composition comprising CoQ10 is administered in the form of a CoQ10 cream at a dosage of CoQ10 between 0.01 mg/cm 2 and 5 mg/cm 2 .
  8. 8 . The method of claim 1 , wherein the pharmaceutical composition comprising CoQ10 is administered with a second composition comprising an additional agent.
  9. 9 . The method of claim 1 , wherein the pharmaceutical composition further comprises an additional agent.
  10. 10 . The method of claim 1 , wherein treatment of the subject results in the reduction of size of one or more blisters and/or wounds by at least about 70% after administration of an effective amount of CoQ10 for a treatment duration of about four weeks.

Description

RELATED APPLICATIONS This application is a continuation application of U.S. application Ser. No. 15/981,831, filed May 16, 2018, allowed, which, in turn, claims priority to U.S. Provisional Application No. 62/507,773 filed on May 17, 2017, the entire contents of which is incorporated by reference in its entirety herein. BACKGROUND OF THE INVENTION According to the Dystrophic Epidermolysis Bullosa Research Association (DebRA), 1 out of every 50,000 babies born are affected with Epidermolysis Bullosa (EB). This is seen across all racial and ethnic groups, and in both sexes equally worldwide. EB comprises a group of genetically determined skin fragility disorders characterized by blistering or tearing of the skin and mucosae following mild mechanical trauma. Traditionally, it was asserted that there were three major groups of inherited EB, namely EB simplex, junctional EB and dystrophic EB; based on the ultrastructural level within which skin cleaves and blisters. (Pearson, R. W., 1988). In 2007, the third international consensus meeting on diagnosis and classification of EB was held in Vienna, Austria. Based on the outcome of this meeting, EB is now classified into 4 major types; mixed type (Kindler syndrome) being the fourth major type. Availability of monoclonal and polyclonal antibodies coupled with advances in molecular diagnostic techniques have led to the sub-classification of EB into at least 30 different subtypes (Fine J D 2010). One hallmark of these conditions is the formation of blisters or wounds which are caused by minor mechanical trauma, friction or heat, with the severity of the disease dependent on the type of EB present. Individuals with EB have significantly delayed healing for the blisters and/or wounds, which are prone to infections. All forms of EB simplex (EBS) have sites that tend to be fragile with a tendency to break and form a lesion within the epidermis (Hanna, Silverman, Boxall, Krafchik, 1983), and generally begin with the disruption of basal keratinocytes. EBS is usually dominantly inherited, and involves disorders of the genes coding keratins 5, 14 and plectin. In rare forms of EBS, there may also be plectin mutations and a likelihood of muscular dystrophy. In contrast, junctional and dystrophic forms of EB are the result of structural breaks within or near the basement membrane zone. In junctional EB (JEB), skin cleavage uniformly develops within the lamina lucida, the narrow electron-sparse upper half of the dermo-epidermal junction. JEB is a recessively inherited disease and involves many genes for components between the epidermis and dermis such as laminin 332, plectin and a6b4-integrin. In dystrophic EB (DEB), cleavage always occurs between the levels of the lamina densa, which is the electrondense lower half of the dermo-epidermal junction (upper dermis). (Fine J D., Schachner L A, 1995). Kindler syndrome accounts for about 1% of EB patients, and involves all layers of the skin having extreme fragility. EB phenotypes are further sub-classified on the basis of the extent of cutaneous involvement (localized versus generalized), the specific nature of the regional distribution of lesions; the types of morphologic lesions present on the skin; the extent (if present) and diversity of extracutaneous disease activity; and the mode of inheritance (autosomal dominant, autosomal recessive). All forms of EB are characterized by a lifetime of recurrent blister and/or wound formation, which linger and often become infected. Blisters can form anywhere on the surface of the skin, including within the oral cavity, surfaces of the eye, in the respiratory tract, gastrointestinal tract and/or the genitourinary tract. In addition to the chronic blisters and wounds, disfiguring scars and disabling musculoskeletal deformities can occur. Some forms of EB are associated with normal longevity. However, several forms of severe EB experience profound morbidity and markedly increased mortality as either a direct or indirect result of the EB. Many people with EB become anemic due to chronic loss of blood through wounds, poor nutritional intake, poor absorption of iron and bone marrow suppression from chronic inflammation. Other patients have selenium and carnitine or vitamin D deficiencies which make them prone to osteoporosis and/or cardiomyopathy. Death often occurs during the first three decades in severely affected patients. Repeated infections in the already nutritionally compromised, anemic patient are usually the cause. Another serious complication in both the dystrophic form and junctional form of EB is the development of aggressive squamous cell carcinomas during young adulthood. Most patients die as the result of widespread metastatic disease, regardless of how early and how aggressively the primary tumors were diagnosed and treated. Tracheolaryngeal obstruction is also a risk for a minority of patients with all forms of junctional EB. Cutaneous involvement (wounds) can range from blisters